Dietary Nondigestible Polysaccharides Ameliorate Colitis by Improving Gut Microbiota and CD4(+) Differentiation, as Well as Facilitating M2 Macrophage Polarization

摘要

Background The aim of this study was to investigate the therapeutic mechanism of a specific multifiber mix diet (MF) designed to match the fiber content of a healthy diet in interleukin-10 knockout (IL-10(-/-)) mice with spontaneous chronic colitis displaying similar characteristics to those of human Crohn's disease (CD). Methods Sixteen-week-old IL-10(-/-) mice were used for the experiments with MF diet for 4 weeks. Severity of colitis, the composition of the fecal microbiota, expression of Th1/Th17 cells, myeloperoxidase (MPO) concentrations, and inflammatory cytokines and chemokines (tumor necrosis factor-alpha [TNF-alpha], IL-6, macrophage inflammatory protein [MIP]-2, monocyte chemoattractant protein-1 [MCP-1], and MIP-1 alpha), as well as arginase 1 (Arg1) and signal transducers and activators of transcription 6 (STAT6) proteins, were measured at the end of the experiment. In addition, the corresponding metabolites (short-chain fatty acids) of MF on CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) were also detected in vivo and in vitro. Results MF treatment significantly ameliorated colitis associated with decreased lamina propria frequency of Th1/Th17 cells, MPO concentrations, and inflammatory cytokines and chemokines (TNF-alpha, IL-6, MIP-2, MCP-1, and MIP-1 alpha). An increase in gut microbial diversity was observed after MF treatment compared with IL-10(-/-) mice, including a significant increase in bacteria belonging to the Firmicutes phylum and a significant decrease in bacteria belonging to the Proteobacteria phylum. Moreover, MF treatment increased the differentiation of CD4(+)CD25(+)Foxp3(+) Tregs mainly by microbial metabolites butyrate. In addition, Arg1 and STAT6 proteins were also significantly increased after MF treatment. Conclusions These results shed light on the contribution of MF treatment to the CD mouse model and suggest that MF has potential as a therapeutic strategy for enhancing efficacy in inducing remission in patients with active CD.